CHARACTERIZATION OF THE GENETIC-DEFECTS IN RECESSIVE TYPE-1 AND TYPE-3 VON-WILLEBRAND-DISEASE PATIENTS OF ITALIAN ORIGIN

The genetic defects causing recessive type 1 and type 3 von Willebrand disease (VWD) in eight families from the northern part of Italy have been investigated. Mutations were identified in 14 of the 16 disease-a ssociated von Willebrand factor (VWF) genes. Only one mutation, a stop codon in exon 45, was previously reported. Several new mutations were identified: one cytosine insertion in exon 42, one guanine deletion i n exon 28, one probably complete VWF gene deletion, one substitution i n the 3' splice site of intron 13, one possible gene conversion, and t hree candidate missense mutations. One missense mutation, the substitu tion of a cysteine in exon 42, was identified in all type 3 VWD patien ts that were previously characterized as a subgroup with significant i ncrease of factor VIII procoagulant activity after desmopressin infusi on. This paper demonstrates again that the molecular defects of quanti tative VWD are diverse and located throughout the entire VWF gene.